Pyridylalkyl thiocarbonates as insect repellents

ABSTRACT

Novel compounds having the formula ##STR1## in which R is alkyl, cycloalkyl, aralkyl, chlorophenyl or chlorobenzyl, R 1  is hydrogen or lower alkyl and n is 1, 2, or 3, are insect repellents.

This invention relates to novel compounds having the formula ##STR2## in which R is alkyl, cycloalkyl, aralkyl, chlorophenyl or chlorobenzyl, R₁ is hydrogen or lower alkyl and n is 1, 2, or 3. If R is hydrogen, the side chain may be substituted on the pyridine ring at the 2-, 3-, or 4-position; if R is lower alkyl the side chain may be substituted at the 2-position.

The term "alkyl" refers to straight- or branched-chain saturated hydrocarbyl moieties having from 1-20, preferably 1-12, carbon atoms. "Lower alkyl" refers to such moieties having from 1-4 carbon atoms. The term "cycloalkyl" refers to cyclic saturated hydrocarbyl moieties having from 3-7 carbon atoms, for instance, cyclohexyl. The term "aralkyl" refers to aromatic moieties, bonded to an aliphatic (straight- or branched-chain) moiety, preferably having from 1-3, most preferably 1 or 2, carbon atoms, for instance, benzyl and phenethyl.

The compounds have utility as insect repellents, particularly for repelling flying insects from lighting and/or feeding.

The compounds of this type can be prepared by reaction of an appropriate pyridyl alkanol with an appropriate chlorothioformate; ##STR3## The pyridyl alkanols in which R is lower alkyl, if not commercially available, can be synthesized, for example, by the method of Umezawa et al., Japanese patent application No. 74/13180.

The reaction is generally conducted at temperatures of about 0° C. to about 25° C. in the presence of a solvent such as methylene chloride and a hydrogen chloride acceptor such as sodium bicarbonate, triethylamine, or pyridine. The product is recovered by conventional extraction, washing, filtration, and other purification steps as may be necessary. Optionally, the hydrogen chloride acceptor may be added after the reaction has gone to completion.

Preparation of such compounds is illustrated by the following example.

Preparation of S-methyl, O-[3-(3-pyridyl)-1-propyl] Thiocarbonate (Compound 1 herein)

In a flask were placed 5.0 grams (g.) (0.0364 mole) 3-(3-pyridyl)-1-propanol and 50 milliliters (ml.) methylene chloride. The flask was cooled to 0° C. There was then added, with stirring, 4.4 g. (0.04 mole) methyl chlorothioformate, at such a rate as to maintain the temperature at a maximum of 15° C. After addition was complete, the mixture was stirred for 1 hour at room temperature.

The product was neutralized with saturated sodium bicarbonate, then washed with water and saturated sodium chloride, and dried over sodium sulfate. The dried solution was filtered and the solvent removed in vacuo, producing 6.2 g. (82% of theoretical yield) of the desired product, a clear, yellow oil, n_(D) ³⁰ 1.5335. The structure of the product was confirmed by infrared (ir), nuclear magnetic resonance (nmr) and mass spectroscopy (ms).

The following Table I contains a list of representative compounds of this invention.

                  TABLE I                                                          ______________________________________                                          ##STR4##                                                                      Compound                     ring                                              No.     R.sub.1    R         position                                                                               n   n.sub.D.sup.30                        ______________________________________                                         1       H        methyl      3-      3   1.5335                                2       H        ethyl       3-      3   1.5420                                3       H        isopropyl   3-      3   1.5110                                4       H        n-propyl    3-      3   1.5165                                5       H        n-butyl     3-      3   1.5115                                6       H        sec.-butyl  3-      3   1.5145                                7       H        isobutyl    3-      3   1.5146                                8       H        tert.-butyl 3-      3   1.5122                                9       H        3-methylbutyl                                                                              3-      3   1.5120                                10      H        n-hexyl     3-      3   1.5077                                11      H        cyclohexyl  3-      3   1.5720                                12      H        C(CH.sub.3).sub.2 C.sub.2 H.sub.5                                                          3-      3   1.5127                                13      H        p-chlorophenyl                                                                             3-      3   1.5838                                14      H        n-dodecyl   3-      3   1.4964                                15      H        benzyl      3-      3   1.5615                                16      H        2-methylbutyl                                                                              3-      3   1.5030                                17      H        ethyl       4-      3   1.5380                                18      methyl   ethyl       2-      3   1.5145                                19      H        methyl      2-      3   1.5610                                20      methyl   methyl      2-      3   1.5191                                21      H        n-propyl    4-      3   1.5126                                22      methyl   n-propyl    2-      3   1.5100                                23      H        isopropyl   4-      3   1.5431                                24      methyl   isopropyl   2-      3   1.5047                                25      H        n-butyl     4-      3   1.5286                                26      methyl   n-butyl     2-      3   1.5029                                27      methyl   sec.-butyl  2-      3   1.5041                                28      H        sec.-butyl  4-      3   1.5016                                29      methyl   isobutyl    2-      3   1.5021                                31      methyl   tert.-butyl 2-      3   1.5027                                32      H        tert.-butyl 4-      3   1.5177                                33      H        methyl      2-      3   1.5230                                34      H        ethyl       2-      3   1.5167                                35      H        isopropyl   2-      3   1.5102                                36      H        n-butyl     2-      3   1.5070                                37      H        sec.-butyl  2-      3   1.5073                                38      H        isobutyl    2-      3   1.5087                                39      H        n-propyl    2-      3   1.5141                                40      H        tert.-butyl 2-      3   1.5067                                41      H        benzyl      4-      3   1.5750                                42      H        benzyl      2-      3   1.5664                                43      methyl   benzyl      2-      3   1.5602                                44      H        phenethyl   2-      3   1.5581                                45      H        phenethyl   4-      3   1.5572                                46      H        phenethyl   3-      3   1.5560                                47      methyl   phenethyl   2-      3   1.5535                                48      H        p-chlorophenyl                                                                             4-      3   1.5766                                49      H        p-chlorophenyl                                                                             2-      3   1.5756                                50      methyl   p-chlorophenyl                                                                             2-      3   1.5742                                51      H        n-octyl     4-      3   1.5018                                52      H        n-octyl     3-      3   1.5023                                53      H        n-octyl     2-      3   1.5015                                54      methyl   n-octyl     2-      3   1.5000                                55      H        tert.-butyl 3-      1   1.5228                                56      H        tert.-butyl 2-      2   1.5011                                57      H        isopropyl   3-      1   1.5191                                58      H        isopropyl   2-      2   1.5125                                59      H        p-chlorobenzyl                                                                             3-      3   1.5603                                ______________________________________                                    

The structures of the compounds in the foregoing Table I were confirmed by ir, nmr, and/or ms.

INSECT REPELLENT TESTS

Compounds described in the above Table I were tested for insect repellency by the following procedures:

Mosquitoes

A paper cup filled with pupae of the mosquito Culex pipiens quinquefasciatus (Say) was placed in a screened cage and the pupae allowed to emerge into adults. Sugar cubes were then saturated with 1.0 milliliter (ml.) of an acetone solution containing 0.1 wt.% of the test compound, and, for a control, with the same amount of acetone alone. After the cubes dried they were put into the screened cage. Repellency was determined by the number of mosquito adults lighting and feeding on the sugar cubes, with observations being made daily for 5 days after treatment. The number of days of complete repellency of mosquitoes from the sugar cubes was recorded.

Comparative tests were similarly conducted using the compound N,N-diethyl-m-toluamide, commercially manufactured and employed as an insect repellent, generally known by the generic name "deet." The results of the tests of deet and the compounds of Table I are shown in the following Table II. The numbers in each column represent the number of days of complete repellency observed using the specified concentration.

                  TABLE II                                                         ______________________________________                                         (Southern House Mosquito)                                                      Compound    Days Repelled, 0.1 wt. %                                           ______________________________________                                         1           11                                                                 2           11                                                                 3           >5                                                                 4           >5                                                                 5           >5                                                                 6           >5                                                                 7           >5                                                                 8           >5                                                                 9           3.5                                                                10          3                                                                  11          3                                                                  12          4.5                                                                13          3                                                                  14          2                                                                  17          1                                                                  18          >3                                                                 19          1                                                                  deet        1                                                                  control     0                                                                  ______________________________________                                    

Houseflies

The insect utilized for this test was the housefly, Musca domestica (L.). One hundred houseflies of mixed sexes were placed in test cages. In each cage was placed a sugar cube saturated with 1.0 ml of acetone containing 1 wt.% of the test compound. The cube was dried and weighed before being placed in the cage. Each cage also contained a water-saturated cotton plug, to provide moisture. The test cages were placed on a turntable and rotated at 1.5 revolutions per minute to keep the flies randomly distributed inside the cage. After 48 hours the flies in each cage were anesthetized with carbon dioxide. The sugar cubes were removed and reweighed and the percentage weight loss (due to consumption by the flies) recorded. A repellency ratio, calculated as the percent weight loss of the treated sugar cube divided by the percent weight loss of a control sugar cube treated with acetone only was calculated. The lower the repellency ratio, the greater the repellency of the test compound. The repellency ratios of the test compounds are shown in the following Table III. Values given for the repellency ratio represent an average of from one to three replications per compound.

                  TABLE III                                                        ______________________________________                                         (Housefly)                                                                     Compound  Repellency Ratio; Concentration, 1 wt. %                             ______________________________________                                         1         0.48                                                                 2         0.37                                                                 3         0.38                                                                 4         0.38                                                                 5         0.39                                                                 6         0.33                                                                 7         0.38                                                                 8         0.37                                                                 9         0.25                                                                 10        0.29                                                                 11        0.40                                                                 12        0.18                                                                 13        0.57                                                                 14        0.66                                                                 17        0.18                                                                 18        0.36                                                                 19        0.42                                                                 20        0.46                                                                 21        0.24                                                                 22        0.36                                                                 23        0.54                                                                 24        0.34                                                                 25        0.38                                                                 26        0.36                                                                 27        0.31                                                                 28        0.19                                                                 29        0.52                                                                 30        0.37                                                                 31        0.35                                                                 32        0.27                                                                 33        0.61                                                                 34        0.37                                                                 35        0.28                                                                 36        0.37                                                                 37        0.18                                                                 38        0.32                                                                 39        0.43                                                                 40        0.31                                                                 41        0.43                                                                 42        0.51                                                                 43        0.64                                                                 44        0.52                                                                 45        0.68                                                                 46        0.37                                                                 47        0.64                                                                 49        0.50                                                                 50        0.55                                                                 51        0.32                                                                 52        0.37                                                                 53        0.54                                                                 54        0.58                                                                 55        0.26                                                                 56        0.37                                                                 57        0.32                                                                 58        0.37                                                                 59        0.35                                                                 deet      0.60                                                                 ______________________________________                                    

Thus at a concentration of 1% by weight, the test compounds repelled insects to the extent that the weight loss of sugar cubes treated with those compounds was generally less than 50% of that of the control (untreated) cubes.

Stable Fly; Yellow Fever Mosquito

Insects utilized for these tests were the stable fly, Stomoxys calcitrans and yellow fever mosquito, Aedes aegypti.

Pupae of these insects were placed in separate standard fly cages and allowed to emerge into adult. The mosquitoes were supplied with a sugar-water solution; the stable flies with water, sugar cubes, and casein. Tests on mosquitoes were performed at least three days after the adults emerged; those on stable flies, one day after emergence because of the short life span (4-5 days) of these flies without a blood meal.

Test compounds were weighed and dissolved in acetone. One milliliter (ml) of the test solution was precipitated onto a 9×9 cm. swatch of cotton stocking. The swatches were then allowed to dry for 1 hour.

A square opening 6×6 cm. was made in an upper corner of one side of each fly cage. A large, hard cardboard disk was placed over the opening so that it could be rotated to either cover or expose the opening as desired. One-half of the disc was left intact. In the remaining half, several 6×6 cm. square openings were cut. When the intact half of this disc was located over the opening in the fly cage, this opening was effectively sealed.

Swatches of treated stocking were placed over the square holes in the disc and held in place by metal frames attached to magnetic tape.

To initiate the test, the disc was rotated so that a treated swatch became located over the opening in the cage. The palm of the tester's hand was placed over a cardboard ring, 8 cm. in diameter and 1 cm. thick. The ring acted as a spacer and protected the hand from bites which could otherwise be inflicted by the insects. A breath of air was exhaled through tubing into the opening, so that insects could be attracted to the swatch by the warm, moist air and the tester's hand. The number of insects landing on the swatch was observed, and the number probing, recorded during a 1-minute exposure. Repellency was considered to occur when 5 or fewer insects probed the swatch during the exposure.

The compounds were tested at applications rates ranging from 0.1 mg/cm² of swatch downwards. The results of these tests on stable flies (SF) and yellow fever mosquitoes (YFM) are contained in Table IV.

                  TABLE IV                                                         ______________________________________                                         (Stable Fly, Yellow Fever Mosquito)                                                          Repellent Concentration, mg/cm.sup.2                             Compound        SF      YFM                                                    ______________________________________                                          1              0.03    0.1                                                     2              0.03    0.1                                                    15              >0.1    >0.1                                                   16              >0.1    >0.1                                                   20              >0.1    >0.1                                                   21              0.1     >0.1                                                   22              >0.1    >0.1                                                   23              >0.1    >0.1                                                   24              >0.1    >0.1                                                   25              >0.1    >0.1                                                   26              >0.1    >0.1                                                   27              >0.1    >0.1                                                   28              >0.1    >0.1                                                   29              >0.1    >0.1                                                   30              >0.1    >0.1                                                   31              >0.1    0.1                                                    32              >0.1    >0.1                                                   33              >0.1    >0.1                                                   34              >0.1    0.03                                                   35              >0.1    0.03                                                   36              >0.1    >0.1                                                   37              >0.1    0.03                                                   38              >0.1    0.03                                                   39              >0.1    0.03                                                   40              >0.1    0.1                                                    41              >0.1    >0.1                                                   42              >0.1    >0.1                                                   43              >0.1    >0.1                                                   44              >0.1    >0.1                                                   45              >0.1    >0.1                                                   46              >0.1    >0.1                                                   47              >0.1    >0.1                                                   48              >0.1    >0.1                                                   49              >0.1    >0.1                                                   50              >0.1    >0.1                                                   51              >0.1    >0.1                                                   52              >0.1    >0.1                                                   53              >0.1    >0.1                                                   54              >0.1    >0.1                                                   59              >0.1    --                                                     ______________________________________                                    

Black Blowfly, Hornfly

Compounds 1 and 2 were tested for repellent activity against the black blowfly, Phormia regina and the hornfly, Haematobia irritans. The blowfly tests were conducted similarly to those on the housefly; the hornfly tests were conducted similarly to those on the stable fly. Results are reported in Table V below.

                  TABLE V                                                          ______________________________________                                                                   Hornfly                                                           Black blowfly,                                                                              repellent                                                         repellency ratio,                                                                           concentration,                                       Compound No. 0.1 wt. %    mg/cm.sup.2                                          ______________________________________                                         1            0.42         0.1                                                  2            0.54         0.03                                                 ______________________________________                                    

The novel compounds of this invention may be used as insect repellents in either diluted or undiluted form. When used in a diluted form, the compounds may be embodied in compositions containing relatively high or relatively low concentrations of the active compound. For example, the active compound can be incorporated into relatively high concentration compositions such as wet sprays or solutions in alcohol or other suitable solvents. Such compositions may contain, in addition to the active compound, adjuvants such as emulsifying agents, surface active agents, anti-oxidants and propellants which may be found normally in insect repellent preparations. The active compounds of this invention may be employed as the sole active component of such compositions or may be used in admixture with other compounds having a similar or different utility. For example, the compounds may be incorporated into creams, lotions, powders, suntan oil, insecticides and other preparations which may contain pesiticidal or other useful substances, as well as into compositions of various types used for treating fabrics or articles of clothing to render them insect repellent. In general, compositions for repellent use may contain from 0.5 to up to 80 weight %, preferably from 2 to about 40 weight %, of the novel active compounds. High concentration formulations, containing up to 95% of the compounds, could also be utilized for low-volume spraying from the air.

Examples of typical formulations employing compounds of this invention are for instance,

                  EXAMPLE 1                                                        ______________________________________                                         Emulsifiable Concentrate                                                       Component            Weight %                                                  ______________________________________                                         Compound 1           53.6                                                      Aromatic Hydrocarbon Solvent                                                                        36.4                                                      Emulsifier           10.0                                                      Total                100.0                                                     ______________________________________                                    

                  EXAMPLE 2                                                        ______________________________________                                         Lotion                                                                         Component           Weight %                                                   ______________________________________                                         Compound 37         10.7                                                       Lanolin             4.8                                                        Mineral oil         8.0                                                        Trihydroxyethylamine stearate                                                                      1.8                                                        Glycosterin         0.8                                                        Glycerine           4.6                                                        Sodium benzoate     1.0                                                        Water               68.3                                                       Total               100.0                                                      ______________________________________                                    

                  EXAMPLE 3                                                        ______________________________________                                         Alcohol Solution                                                               Component      Weight %                                                        ______________________________________                                         Compound 38    53.6                                                            Isopropanol    46.4                                                            Total          100.0                                                           ______________________________________                                    

                  EXAMPLE 4                                                        ______________________________________                                         Alcohol Solution                                                               Component      Weight %                                                        ______________________________________                                         Compound 39    80.0                                                            Ethanol        20.0                                                            Total          100.0                                                           ______________________________________                                    

                  EXAMPLE 5                                                        ______________________________________                                         Wettable Powder                                                                Component            Weight %                                                  ______________________________________                                         Compound 2           26.9                                                      Hydrated calcium silicate                                                                           62.1                                                      Sodium lignosulfonate                                                                               5.0                                                       Orzan A (mixture of ammonium                                                                        5.0                                                       lignosulfonate and wood                                                        sugars)                                                                        Wetting agent        1.0                                                       Total                100.0                                                     ______________________________________                                     

What is claimed is:
 1. A compound having the formula ##STR5## in which R is alkyl, cycloalkyl, aralkyl, wherein alkyl is a group containing up to 20 carbon atoms chlorophenyl or chlorobenzyl, R₁ is hydrogen or lower alkyl, and n is 1, 2, or
 3. 2. A compound according to claim 1 in which R₁ is hydrogen.
 3. A compound according to claim 1 in which R₁ is methyl.
 4. A compound according to claim 1 in which R is alkyl wherein alkyl is a group containing up to 20 carbon atoms.
 5. A compound according to claim 1 in which the side chain is substituted on the pyridine ring at the 2-position.
 6. A compound according to claim 1 in which the side chain is substituted on the pyridine ring at the 3-position.
 7. A compound according to claim 1 in which the side chain is substituted on the pyridine ring at the 4-position.
 8. A compound according to claim 1 in which R₁ is hydrogen, R is methyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 9. A compound according to claim 1 in which R₁ is hydrogen, R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 10. A compound according to claim 1 in which R₁ is hydrogen, R is isopropyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 11. A compound according to claim 1 in which R₁ is hydrogen, R is n-propyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 12. A compound according to claim 1 in which R₁ is hydrogen, R is n-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 13. A compound according to claim 1 in which R₁ is hydrogen, R is sec.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 14. A compound according to claim 1 in which R₁ is hydrogen, R is isobutyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 15. A compound according to claim 1 in which R₁ is hydrogen R is tert.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 16. A compound according to claim 1 in which R₁ is hydrogen, R is 3-methylbutyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 17. A compound according to claim 1 in which R₁ is hydrogen, R is n-hexyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 18. A compound according to claim 1 in which R₁ is hydrogen, R is cyclohexyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 19. A compound according to claim 1 in which R₁ is hydrogen, R is C(CH₃)₂ C₂ H₅, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 20. A compound according to claim 1 in which R₁ is hydrogen, R is p-chlorophenyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 21. A compound according to claim 1 in which R₁ is hydrogen, R is n-dodecyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 22. A compound according to claim 1 in which R₁ is hydrogen, R is benzyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 23. A compound according to claim 1 in which R₁ is hydrogen, R is 2-methylbutyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 24. A compound according to claim 1 in which R₁ is hydrogen R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 25. A compound according to claim 1 in which R₁ is methyl, R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 26. A compound according to claim 1 in which R₁ is hydrogen, R is methyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 27. A compound according to claim 1 in which R₁ is methyl, R is methyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 28. A compound according to claim 1 in which R₁ is hydrogen, R is n-propyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 29. A compound according to claim 1 in which R₁ is methyl, R is n-propyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 30. A compound according to claim 1 in which R₁ is hydrogen, R is isopropyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 31. A compound according to claim 1 in which R₁ is methyl, R is isopropyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 32. A compound according to claim 1 in which R₁ is hydrogen, R is n-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 33. A compound according to claim 1 in which R₁ is methyl, R is n-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 34. A compound according to claim 1 in which R₁ is methyl, R is sec.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 35. A compound according to claim 1 in which R₁ is hydrogen, R is sec.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 36. A compound according to claim 1 in which R₁ is methyl, R is isobutyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 37. A compound according to claim 1 in which R₁ is hydrogen, R is isobutyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 38. A compound according to claim 1 in which R₁ is methyl, R is tert.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 39. A compound according to claim 1 in which R₁ is hydrogen, R is tert.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 40. A compound according to claim 1 in which R₁ is hydrogen, R is methyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 41. A compound according to claim 1 in which R₁ is hydrogen, R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 42. A compound according to claim 1 in which R₁ is hydrogen, R is isopropyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 43. A compound according to claim 1 in which R₁ is hydrogen, R is n-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 44. A compound according to claim 1 in which R₁ is hydrogen, R is sec.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 45. A compound according to claim 1 in which R₁ is hydrogen, R is isobutyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 46. A compound according to claim 1 in which R₁ is hydrogen, R is n-propyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 47. A compound according to claim 1 in which R₁ is hydrogen, R is tert.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 48. A compound according to claim 1 in which R₁ is hydrogen, R is benzyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 49. A compound according to claim 1 in which R₁ is hydrogen, R is benzyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 50. A compound according to claim 1 in which R₁ is methyl, R is benzyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 51. A compound according to claim 1 in which R₁ is hydrogen, R is phenethyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 52. A compound according to claim 1 in which R₁ is hydrogen, R is phenethyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 53. A compound according to claim 1 in which R₁ is hydrogen, R is phenethyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 54. A compound according to claim 1 in which R₁ is methyl, R is phenethyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 55. A compound according to claim 1 in which R₁ is methyl, R is p-chlorophenyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 56. A compound according to claim 1 in which R₁ is hydrogen, R is p-chlorophenyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 57. A compound according to claim 1 in which R₁ is methyl, R is p-chlorophenyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 58. A compound according to claim 1 in which R₁ is hydrogen, R is n-octyl, n is 3 and the side chain is substituted on the pyridine ring at the 4-position.
 59. A compound according to claim 1 in which R₁ is hydrogen, R is n-octyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 60. A compound according to claim 1 in which R₁ is hydrogen, R is n-octyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 61. A compound according to claim 1 in which R₁ is methyl, R is n-octyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 62. A compound according to claim 1 in which R₁ is hydrogen, R is tert.-butyl, n is 1 and the side chain is substituted on the pyridine ring at the 3-position.
 63. A compound according to claim 1 in which R₁ is hydrogen, R is tert.-butyl, n is 2 and the side chain is substituted on the pyridine ring at the 2-position.
 64. A compound according to claim 1 in which R₁ is hydrogen, R is isopropyl, n is 1 and the side chain is substituted on the pyridine ring at the 3-position.
 65. A compound according to claim 1 in which R₁ is hydrogen, R is isopropyl, n is 2 and the side chain is substituted on the pyridine ring at the 2-position.
 66. A compound according to claim 1 in which R₁ is hydrogen, R is p-chlorobenzyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 67. A method of repelling insects from a locus to be protected therefrom, comprising applying to said locus an effective insect repelling amount of a compound having the formula ##STR6## in which R is alkyl, cycloalkyl, aralkyl, wherein alkyl is a group containing up to 20 carbon atoms chlorophenyl or chlorobenzyl, R₁ is hydrogen or lower alkyl, and n is 1, 2, or
 3. 68. A method according to claim 67 in which R₁ is hydrogen.
 69. A method according to claim 67 in which R₁ is methyl.
 70. A method according to claim 67 in which R is alkyl wherein alkyl is a group containing up to 20 carbon atoms.
 71. A method according to claim 67 in which the side chain is substituted on the pyridine ring at the 2-position.
 72. A method according to claim 67 in which the side chain is substituted on the pyridine ring at the 3-position.
 73. A method according to claim 67 in which the side chain is substituted on the pyridine ring at the 4-position.
 74. A method according to claim 67 in which the insect is the housefly.
 75. A method according to claim 67 in which the insect is yellow fever mosquito.
 76. A method according to claim 67 in which the insect is stable fly.
 77. A method according to claim 67 in which R is methyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 78. A method according to claim 67 in which R is ethyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.
 79. A method according to claim 67 in which R is ethyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 80. A method according to claim 67 in which R is isopropyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 81. A method according to claim 67 in which R is sec.-butyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 82. A method according to claim 67 in which R is isobutyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 83. A method according to claim 67 in which R is n-propyl, R₁ is hydrogen, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.
 84. An insect repellent composition comprising:(a) an amount of a compound having the formula ##STR7## in which R is alkyl, cycloalkyl, aralkyl wherein alkyl is a group containing up to 20 carbon atoms, chlorophenyl or chlorobenzyl, R₁ is hydrogen or lower alkyl, and n is 1, 2, or 3, effective to repel insects; and (b) an inert diluent or carrier suitable for insect repellent use. 